@article{96b966eb26a6411a857b971f0d088f4b,
title = "Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells",
abstract = " Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f + long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors. LT-HSC reprogramming can follow multiple paths and is most efficient when transduction is performed after the cells have exited G 0 . Sequencing of 75 paired skin fibroblasts/LT-HSC samples collected from nine individuals revealed that LT-HSCs contain a lower load of somatic single-nucleotide variants (SNVs) and indels than skin fibroblasts and accumulate about 12 SNVs/year. Mutation analysis revealed that LT-HSCs and fibroblasts have very different somatic mutation signatures and that somatic mutations in iPSCs generally exist prior to reprogramming. LT-HSCs may become the preferred cell source for the production of clinical-grade iPSCs.",
keywords = "induced pluripotent stem cells, long-term hematopoietic stem cells, reprogramming, skin fibroblasts, somatic mutation",
author = "Kai Wang and Guzman, {Anthony K.} and Zi Yan and Shouping Zhang and Hu, {Michael Y.} and Hamaneh, {Mehdi B.} and Yu, {Yi Kuo} and Seda Tolu and Jinghang Zhang and Kanavy, {Holly E.} and Kenny Ye and Boris Bartholdy and Bouhassira, {Eric E.}",
note = "Funding Information: E.E.B., K.W., Z.Y., S.Z., B.B., and E.E.B. were supported by NYSTEM grants C030135 and C029154; NIH grant HL130764; and Doris Duke Foundation grant 2017087. M.B.H. and Y.-K.Y. are supported by the Intramural Research Program of the NIH, National Library of Medicine. We thank Daqian Sun and Swathi-Rao Narayanagari from the Stem Cell Flow Cytometry and Xenotransplantation Facility for expert help with flow sorting and xenotransplantation. We thank the Einstein Flow Cytometry Core Facility for expert help on flow sorting. We thank Rob Durbin from the Einstein Epigenomic Core for help with bioinformatics. Funding Information: E.E.B., K.W., Z.Y., S.Z., B.B., and E.E.B. were supported by NYSTEM grants C030135 and C029154 ; NIH grant HL130764 ; and Doris Duke Foundation grant 2017087 . M.B.H. and Y.-K.Y. are supported by the Intramural Research Program of the NIH , National Library of Medicine . We thank Daqian Sun and Swathi-Rao Narayanagari from the Stem Cell Flow Cytometry and Xenotransplantation Facility for expert help with flow sorting and xenotransplantation. We thank the Einstein Flow Cytometry Core Facility for expert help on flow sorting. We thank Rob Durbin from the Einstein Epigenomic Core for help with bioinformatics. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = mar,
day = "5",
doi = "10.1016/j.celrep.2019.02.021",
language = "English (US)",
volume = "26",
pages = "2580--2592.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}